This document discusses rehabilitation principles for multiple sclerosis (MS). It begins by defining MS as a chronic, progressive disease of the central nervous system characterized by demyelination of the brain and spinal cord. It then covers the epidemiology, pathogenesis, subtypes, common symptoms and signs, diagnosis using the McDonald criteria, disease severity as measured by EDSS, disease-modifying therapies, and approaches to managing common issues like gait impairment and fatigue through rehabilitation and exercise.

1. D R R A V I K H A T R I
3 R D Y E A R R E S I D E N T
M D P M & R
S M S M E D I C A L C O L L E G E A N D H O S P I T A L
J A I P U R
Rehabilitation Principles in
Multiple Sclerosis
PMR PG Teaching Sept 2016

2. DEFINITION
 MS is a chronic progressive disease of the central nervous
system.
 Brain and spinal cord are characterized by multiple areas of
white matter demyelination (inflammation).
 These inflammatory sites lead to plaque formation that may
recur and enlarge with subsequent exacerbations and remissions.

3. Epidemiology
 MS is the third leading cause of significant disability in the 20–
50 age range
 The exact cause is unknown
 It affects F>M 2:1, Whites>>>>Blacks, Asians (Middle-aged
adults)
 There is an increased incidence in the higher socioeconomic class
(+) Family history involving siblings > parents (4–5%)

4. Cont…
 Although females have a higher risk of having MS, those males
who are affected tend to have a more aggressive course, difficulty
with recovery after attack, and more rapid accumulation of
disability.

5. Pathogenesis
Genetic Linkage
MS is thought to be an autoimmune disease in which
immune and inflammatory cells attack the CNS, damaging the
myelin, axons, and neurons.
Genetic Risk of Multiple Sclerosis

6. Cont…
Environmental Factors
 The incidence of MS increased with distance from the equator.
 The effects of vitamin D have demonstrated that reduced levels
of vitamin D increases the risk of MS development, particularly
in whites.
 Twenty minutes of whole-body sun exposure equates to
approximately 10,000 International Units of vitamin D.
 More research supports changing the minimum daily
consumption of vitamin D because it is found to be protective in
several other diseases.

7. Cont…
Other Factors
 A BMI of >20 increases the risk of MS and a BMI ≥27 increased
the risk by twofold. Obese females between 10 and 20 years old
seem to be at greater risk than males during the same time
period.
 Increased clinical and radiologic activity with increased sodium
intake has been suggested as another cause of MS.

8. Cont…
Immunology
 The pathologic hallmarks of acute MS lesions are perivenular
immune cell infiltrate, demyelination, myelin laden
macrophages, edema, and axonal damage.
 Relapses in MS are thought to be mediated by CNS-targeting
peripherally activated helper lymphocytes.
 These autoreactive lymphocytes could have been activated
through “molecular mimicry,” in which foreign antigens (e.g.,
viral or bacterial proteins) that are similar to CNS antigens
activate the lymphocytes that will eventually react against the
self-antigens.

9. Cont…
 On the other hand, antigens leaked from the CNS, probably
resulting from a previous unknown insult, can trigger the
immune response by activating CD4+ helper T cells. These cells
facilitate the recruitment and activation of other immune cells—
for example, monocytes and macrophages, B cells, CD8+
cytotoxic T cells, and natural killer cells.
 It is not clear which autoantigen(s) ignite the autoimmune
process in MS.

11. Subtypes
Relapsing-remitting MS (RR-MS)
 More than 80% of the cases
 Defined clinical exacerbation of neurological symptoms
 Followed by complete or incomplete remission during which the
person fully or partially recovers from the deficits acquired
during relapse

12. Cont…
Primary-progressive MS (PP-MS)
 10 to 20% of individuals with MS are diagnosed with PP-MS
 Gradual progression of the disease from its onset
 No overlapping relapses and remissions

13. Cont…
Progressive-relapsing MS (PR-MS)
 Rare
 Initially presenting as PP-MS however, during the course of the
disease the individuals develop true neurologic exacerbations
 Steady progression of clinical neurological damage with
superimposed relapses and remissions.

14. Cont…
Secondary Progressive MS (SP-MS)
 SP-MS is characterized by a steady progression of neurological
damage with or without superimposed relapses and minor
remissions
 Individuals with SP-MS will have experienced a period of RR-
MS, which may have lasted from 2 to 40 years
 Any super-imposed relapses and remissions fade over time

15. PROGNOSTIC FACTORS

16. Common symptoms
 Bladder and Bowel dysfunction
 Fatigue ( Central in nature)
 Pain
 Visual disturbances: Optic neuritis, diplopia, nystagmus
 Cerebellum and basal ganglia: ataxia, intention tremor
 Doral column: Sensory abnormalities (paresthesias), impairment
of deep sensation, proprioception

17. Cont…
 Corticospinal tract: Weakness and spasticity
 Frontal lobe dysfunction: Cognitive, memory, learning, and
impaired emotional responses, depression
 Speech abnormalities: Dysarthria
 Brainstem abnormalities: Deafness, tinnitus, vertigo, vomiting,
transient facial anesthesia, dysphagia

18. Common signs
Lhermitte’s sign: Classic but not pathognomonic.
Passive neck flexion causing an electric shock-like sensation
radiating to the spine, shoulders as well as other areas. This sign
is most likely a result of the increased sensitivity of the myelin to
stretch or traction
Uhthoff's phenomenon is the worsening of neurologic
symptoms in multiple sclerosis and other neurological,
demyelinating conditions when the body gets overheated from
hot weather, exercise, fever, or saunas and hot tubs.

19. Diagnosis
 Because of the similarity MS has to various other neurologic,
rheumatologic, and vascular diseases, MS remains a diagnosis of
exclusion.
 It is important to distinguish and exclude other demyelinating
disorders, including neuromyelitis optica (NMO), acute
transverse myelitis, and acute disseminated encephalomyelitis
(ADEM).

20. Cont…
 Criteria for diagnosis of NMO include both optic neuritis and
acute myelitis, plus two of the following three factors: contiguous
spinal cord involvement spanning three spinal segments or
more, exclusion of MS, and NMO–immunoglobulin G (IgG)
seropositive status.
 Acute transverse myelitis presents acutely, may be monophasic
or multiphasic, and has a clearly defined sensory level with
exclusion of other causes. It is a focal inflammatory disorder of
the spinal cord and may result in abnormalities in motor,
sensory, or autonomic function.

21. Cont…
 MRI is recommended for the diagnostic evaluation in MS.
 The International Panel on Diagnosis of MS (the Panel)
recommends screening with MR sequencing.
 The McDonald criteria are the most current and widely used to
diagnose MS.

22. Cont…
 Dissemination in space is met by having one or more T2 lesions
in two out of four locations in the CNS:
periventricular
juxtacortical
infratentorial, and
spinal cord
 Dissemination in time was met by the presence of a new T2
and/or gadolinium-enhancing lesion on a follow-up MRI,
irrespective of the timing or the simultaneous presence of
asymptomatic gadolinium-enhancing lesions and nonenhancing
lesions

23. 2010 Revised McDonald Diagnostic Criteria for Multiple
Sclerosis

24. EDSS is a method of quantifying disability
in multiple sclerosis based on eight Functional
Systems (FS)
Expanded Disability Status Scale (EDSS)
•Pyramidal (ability to walk)
•Cerebellar (coordination)
•Brain stem (speech and swallowing)
•Sensory (touch and pain)
•Bowel and bladder functions
•Visual
•Mental
•Other (any other neurological findings)
Normal
Neurological Exam
0.0
Death due to MS10.0
1.0
4.5
5.0
9.5
Fully ambulatory
Ambulation
impairment
A graph showing the average time a person spends in each EDSS level.

25. Disease-Modifying Therapies for Multiple Sclerosis

26. Rehabilitation, Exercise, and Symptom
Management

27. Physical Activity
 A person with a disability is prone to inactivity and
deconditioning.
 Current recommendations for physical activity are meant for
individuals without physical disability and those guidelines are
often not applicable to the population with disabilities.
 Exercise is helpful for PwMS with no evidence for deleterious
effect. The intensity, duration, and frequency must be coupled
with a patient’s symptoms, heat intolerance, strength, and
endurance.

28. Canadian Physical Activity Guidelines for Adults with
Multiple Sclerosis

29. Gait Impairment
 Mobility impairment is one of the most common single
disabilities in PwMS.
 Approximately 75% of PwMS have mobility challenges.
 There is an increased risk of weakness, spasticity, contractures,
bone mineral changes, cardiovascular changes, reduced
independence, and reduced quality of life. Overall, long-term
positive prognostic indicators for disability and gait impairment
include female gender, young age, complete recovery of initial
exacerbation (specific to the RRMS subtype), and reduced
relapse rate in the first 5 years.

30. Cont…
 The Timed 25 (T25) Foot Walk Test is a validated measure of
walking speed in MS. A 20% change in walking speed is
considered significant and clinically meaningful.
 Other gait tests, such as the Two- and Six- Minute Walking Tests
have demonstrated correlation to ambulation and physical
fatigue in PwMS.
 Dalfampridine was approved for the use of PwMS with walking
impairment in 2010 based on the results of two phase III
randomized, placebo-controlled trials. Approximately one third
of participants displayed 25% improvement in their Timed 25
walking speed.

31. Cont…
 Dalfampridine is given at a dose of 10 mg every 12 hours.
 A history of seizures is an absolute contraindication because
dalfampridine lowers the seizure threshold.
 Other adverse events include increased frequency of urinary tract
infections, vertigo, insomnia, headache, and falls.
 Dalfampridine is renally excreted; therefore, a baseline basic
metabolic panel is advised because adequate creatinine clearance
(51 to 80 mL/min) is vital.

32. Fatigue
 Fatigue remains one of the most common and debilitating
symptoms in MS and is quoted as one of the single most
disabling symptoms.
 Patients commonly describe fatigue as a “reversible motor and
cognitive impairment, with reduced motivation and desire to
rest.”
 Individuals with MS may experience two types of fatigue:
peripheral and central. Peripheral fatigue is associated with
fatigability, that is, a generalized sense of exhaustion affecting
the patient after a few minutes of physical activity and is
alleviated with rest.

33. Cont…
 Central fatigue is subjective and is associated with dysfunction in
arousal and attention. The individual reports a feeling of
constant exhaustion or lassitude that can lead to worsening
vision or function. Rest will not have an effect on central fatigue
and thereby has a significant impact on function, quality of life,
relationships, and even maintenance of occupation/vocation.

34. Cont…
 Awareness of triggering factors such as heat, stress, or
overexertion should be emphasized. Also, energy conservation
techniques and training are advised.
 In addition to energy conservation and avoidance of triggers,
pharmacologic treatment is advised to help maintain energy and
focus.

35. Adult Doses for Fatigue Treatment

36. Sleep Disorders
 Approximately 10% of the general population suffers from
insomnia, whereas approximately 40% to 50% of PwMS report
difficulty with sleep initiation, maintenance, or have early
morning awakening.
 Symptoms of MS that may interfere with sleep include spasticity,
pain/paresthesias, and nocturia.
 Treatment agents include zolpidem, trazodone, benzodiazepine,
sedating antidepressants, and antihistamines.

37. Cont…
 Sleep-disordered breathing, obstructive sleep apnea, and central
sleep apnea may be the etiology of persistent fatigue in PwMS.
 Obstructive sleep apnea is a result of upper airway obstruction
during sleep.
 Central sleep apnea is the lack of respiratory effort during sleep.
 Patients with clinical or radiologic evidence of brainstem
involvement had elevated Apnea-Hypopnea Index (episodes of
obstructive apneas, central apneas, or hypopneas per hour of
sleep) than those without brainstem involvement.

38. Cont…
 Besides obstructive sleep apnea and central sleep apnea, other
sleep-related movement disorders include restless leg syndrome
(RLS) and periodic limb movement disorder (PLMD).
 Patients with RLS should undergo screening for iron deficiency
because this may contribute to symptoms. Treatment for both
RLS and PLMD includes dopaminergic agents, benzodiazepine
(clonazepam), and anticonvulsants.

39. Mood Disorders
 The most common mood disorder in MS is depression. It is present in
at least 50% of patients.
 The lifetime prevalence of depression in MS is three times that of the
general population.
 The overlap of symptoms in both depression and MS (fatigue, poor
concentration, sleepiness/ fatigue, and appetite disturbance) can lead
to underdiagnosis of depression and has delayed the diagnosis of MS.
 Screening for DMT-related side effects, particularly IFNs, is advised.
Some patients may have mood disorders secondary to DMT and may
benefit from a change.

40. Thermoregulation
 The pathophysiology of MS is one of central demyelination.
 Physiatrists are keenly aware of the effects of segmental demyelination:
reduction in conduction velocity, altered saltatory conduction, and
eventual conduction block.
 The safety factor (ratio of action current available at a node to
threshold current) is responsible for successful conduction. Advanced
demyelination reduces the safety factor.
 Heat causes alteration of the sodium channels and also reduces the
safety factor and amplitude of nerve action potentials. A demyelinated
nerve is more vulnerable to heat-related changes than the unaffected
nerve.

41. Cont…
 Heat intolerance is a well-established symptom in PwMS.
 Uhthoff phenomenon, a transient loss of vision or blurred vision,
after a hot bath or exercise is common.
 Heat causes transient worsening of many symptoms of MS and
can cause fatigue.
 The “Hot Bath Test” was used before the availability of MRI to
diagnose patients with MS.

42. Cont…
 Exposure to heat can cause worsening of both physical and
cognitive function. Autonomic dysfunction also contributes to
poor temperature regulation in PwMS.
 Patients should be counseled about prevention and treatment
options to prevent potentially fatal injuries from occurring.
 Avoidance of warm baths or swimming in heated pools is
advised. In general, water temperatures no greater than 84° F
(26.7 to 28.9° C) is advised.

43. Spasticity
 Spasticity affects up to 85% of PwMS. Lower limb spasticity is
much more common (97%) than upper limb spasticity (50%).
 Oral baclofen is the usual first-line oral agent. Tizanidine may be
limited given its sedating side effects. Clonazepam is helpful in
cases of PLMD or nighttime spasms.
 The benefit of chemodenervation with botulinum toxin (BoNT)
injections in MS is paramount, resulting from the difficulty with
tolerance of oral antispasmodics.

44. Cont…
 Intrathecal baclofen (ITB) therapy via an implanted drug delivery
device is indicated when oral or injectable treatment becomes
ineffective. The clinician is encouraged to use this therapy before the
onset of significant walking impairment or lower limb weakness.
 The use of ITB pumps in patients with MS has demonstrated
improvements in spasticity, quality of life, sleep quality, bowel and
bladder performance, skin integrity, and ambulation with low
complication rates.
 Phenol injections or surgical intervention may be used in patients with
severe mobility or contractures and have failed conservative therapies.

45. Pain
 Patients with MS experience neuropathic and nociceptive pain.
Prevalence studies report that 29% to 86% of patients are
affected by pain.
 Neuropathic pain arising as a direct consequence of a lesion or
disease that affects the somatosensory system.
 Nociceptive pain is attributable to stimulation of nociceptors that
signal tissue irritation or injury to elicit an appropriate response.
Pain negatively impacts mood, energy, daily activities, vocation,
social interaction, and has been linked with reduced quality of
life in PwMS.

46. Cont…
 Neuropathic pain has a prevalence of 50% in MS and is believed
to be a result of the presence of plaques in the CNS (particularly
the corticospinal and dorsal column tracts), causing symptoms of
allodynia and hyperalgesia.
 Patients respond well to anticonvulsant treatment, particularly
gabapentin.
 Another agent in the same class is pregabalin. Although effective
for its treatment effect, its side effect profile is difficult for some
patients (edema, sedation, weight gain, constipation).

47. Cont…
 Other agents in the anticonvulsant class include levetiracetam,
lamotrigine, and zonisamide.
 The tricyclic antidepressant class may also be used to treat
neuropathic pain; again, the side effect profile (dry mouth,
constipation, drowsiness, urinary retention) may pose a
challenge for patients.
 Patients who are unable to tolerate the side effects or obtain
clinically meaningful relief from oral medications may consider
intrathecal therapy.

48. Cont…
 Morphine and ziconotide are both approved for management of
neuropathic pain via intrathecal infusion.
 Ziconotide is a nonopioid agent and demonstrated significant
pain reduction over placebo.It selectively targets voltage-gated
calcium channels and prevents primary afferent transmission of
pain signals in the spinal cord.
 Common side effects of Ziconotide include dizziness, nausea, and
confusion. It is a viable option for patients that are not opioid
responsive and does not cause tolerance, dependence, or
respiratory depression.

49. Cont…
 Trigeminal neuralgia (TN) affects approximately 2% to 6% of
patients with MS and is 20 times more common in PwMS.
 It may be a result of focal compression of the trigeminal nerve
root near its entry at the pons (primary TN) or as a result of a
neurologic diagnosis such as demyelinating plaques in the same
region or a posterior fossa tumor (symptomatic TN).
 Patients complain of spontaneous, unilateral, lancinating
“electrical sparks.” Light, tactile sensation or pressure may
stimulate the pain.
 The pain can last for seconds to hours.

50. Cont…
 Treatment options include anticonvulsants (carbamazepine,
gabapentin, lamotrigine, topiramate), antispasmodics (baclofen),
and in rare instances, narcotics.
 Again, most PwMS are hesitant to take opiates because of the
cognitive and physical clouding that may occur.
 Finally, misoprostol, a prostaglandin E analogue relieved pain in
patients with TN and should be considered.
 Misoprostol is believed to be effective because the T cell
inhibition caused by prostaglandins leads to an antiinflammatory
effect in plaques.

51. Cont…
 Doses of misoprostol ranged from 100 to 200 mg titrated up to
four times a day.
 Patients refractory to or unable to tolerate oral medications may
consider BoNT injections or neurosurgery referral for
microvascular decompression, rhizotomy, or gamma knife
repair.
 “MS hug” is described by patients as a feeling of tightness across
their ribs, as if they were being hugged very tightly.

52. Cont…
 The cause of “MS hug” is unknown.
 Burning and tingling sensations are common.
 Treatment with anticonvulsants or topical compound mixtures of
anticonvulsants and lidocaine are suggested.

53. Neurogenic Bladder, Neurogenic Bowel, and
Sexual Dysfunction

54. Neurogenic Bladder
 The presence of lesions in the brain and/or spinal cord may lead
to disorders of emptying (double voiding, incomplete emptying,
slow or intermittent stream), storage (urinary urgency,
frequency, nocturia, incontinence), or a mixture of both
(detrusor sphincter dyssynergia).
 It affects up to 75% of PwMS.
 Treatment includes pelvic muscle training, medication, BoNT
injection, and surgery.

55. Cont…
 Pharmacologic treatment consists of antimuscarinic agents for
treating disorders of storage.
 α-Antagonists are commonly recommended for treatment of
voiding disorders.
 Desmopressin may be indicated for symptoms of nocturia.
 BoNT type A (BoNT-A), specifically Onabotulinum Toxin, is
FDA-approved for the treatment of neurogenic detrusor
overactivity in PwMS. Intravesical injections of BoNT-A have
been found to increase the bladder capacitance and reduce
episodes of urinary incontinence.

56. Cont…
 The benefits have been reported to last up to 8 to 10 months,
although injections may be performed every 6 months.
 Patients should be advised of a possible need to catheterize post
injection if post void residuals are elevated.
 Nerve stimulation has also been evaluated for treating
neurogenic bladder disorders.

57. Cont…
 Posterior tibial nerve stimulation involves needle insertion
superior and medial to the medial malleolus with stimulation
sufficient to induce toe flexion and tingling distal to and
including the ankle.
 The procedure is indicated in patients who failed or are unable to
tolerate conservative treatment for overactive bladder and
typically involves 12 × 30-minute weekly sessions.
 The use of posterior tibial nerve stimulation demonstrated a
clear reduction in urinary incontinence, urgency, frequency, and
number of incontinence pads used.

58. Cont…
 Sacral nerve stimulation is another option for the treatment of
hyperreflexia, urge incontinence, and urgency/ frequency
disorders.
 The exact mechanism of action is unknown, but it is believed to
restore the balance between excitatory and inhibitory
stimulation of the sacral and suprasacral regions.
 A trial period is advised for 3 to 7 days with pretrial and posttrial
voiding diary evaluation for effectiveness.
 This is a surgical procedure and its use in MS is limited because
of limited MRI compatibility of the devices.

59. Neurogenic Bowel
 Neurogenic bowel presents as constipation or fecal incontinence.
 Constipation is believed to be caused by immobilization or
abnormal colonic contractility, tone, or recto-anal reflexes.
 Fecal incontinence may be attributable to loss of control of the
external anal sphincter, abnormal recto-sigmoid compliance, or
recto-anal reflexes.
 The use of probiotics can help both constipation and
incontinence.

60. Sexual Dysfunction
 Sexual dysfunction (SD) is present in approximately 42% to 90%
of PwMS.
 Women commonly report decreased libido and loss of
lubrication. Men report erectile and ejaculatory dysfunction.
Both sexes report challenges with achieving orgasm.
 Primary SD may be caused by CNS demyelination that directly
impairs sexual feelings and/or the response. This includes
symptoms of decreased or loss of libido, paresthesias that make
the sexual encounter painful or unpleasurable.

61. Cont…
 Secondary SD is attributable to disability secondary to MS, and
are items that indirectly affect the sexual response. This may
include neurogenic bladder or bowel symptoms, spasticity,
tremor, or immobility.
 Tertiary SD involves one’s view of self and the psychological
impact that culture and society place on sex and intimacy. Family
dynamics, interpersonal conflict, poor self-esteem, and altered
views of one’s body image are included.

62. Cont…
 Management includes education and communication.
 Reducing the dependence on medications for side effects that
impair libido or energy as well as using medications that reduce
spasms or pain may be needed.
 Sildenafil citrate is effective for male patients with erectile
dysfunction.
 Women with SD were trialed on sildenafil citrate for
improvement in sexual response, blood flow, and improved
neurophysiologic response.

63. Cognitive Impairment
 Cognitive impairment (CI) may be present at any stage of MS.
Approximately 40% to 70% of patients have CI.
 Impairments that are commonly seen in PwMS include episodic
memory loss, attention deficits, delayed processing speed, and
difficulty in executive function. Dementia is less commonly
present in MS.
 Various structural factors on MRI have correlated with CIs in
PwMS. Increased cortical atrophy, widening of the third
ventricle, and overall loss of brain volume are seen in persons
with CI.

64. Cont…
 Factors that may affect CI include disease duration, MS subtype,
level of disability, and pre-morbid level of verbal competence.
One striking feature is the concomitant presence of depression or
depressive symptoms in patients with CI.
 Subcutaneous IFN-β1a and IFN-β1b can stabilize or delay the
progression of CI in persons with RRMS.
 One year of natalizumab treatment actually demonstrated
significant improvement in cognitive performance and fatigue in
patients with RRMS.

65. Cont…
 In addition to DMT, cognitive behavioral therapy has reduced
distress and improved cognitive performance in several small
studies.

66. Swallowing
 Dysphagia, or difficulty with swallowing liquids or solids, may
present at any stage of MS.
 An estimated 33% to 43% of patients are affected.
 The prevalence of dysphagia increases with increasing disability.
 The etiology of dysphagia in MS is likely to be attributable to the
involvement of cortico-bulbar, cerebellar, or brainstem regions.
 Treating dysphagia with compensatory strategies is often
effective.

67. Cont…
 This includes (1) postural changes, (2) modifying the amount of
food bolus consumed, and (3) changing the food consistency.
 Other treatments include electrical stimulation and neurotoxin
injection.
 Pharyngeal electrical stimulation to treat oropharyngeal
dysphagia significantly reduces the amount of penetration and
aspiration.
 Injection of BoNT into the cricopharyngeal muscle has been
reported to be effective for the treatment of upper esophageal
hyperactivity.

68. Pseudobulbar Affect
 Pseudobulbar affect (PBA) is a disorder of uncontrollable
laughter or crying that is incongruent with the social or
professional situation.
 Although PBA can be seen in almost any illness, this is
commonly seen in persons with neurologic disorders including
MS, amyotrophic lateral sclerosis, stroke, and traumatic brain
injury.
 Prevalence in MS is believed to be 6.5% to 46.26%.

69. Cont…
 Patients who suffer from this may feel socially isolated resulting
from the lack of control over their laughing or crying episodes.
PBA should be differentiated from depression in which one’s
mood is congruent to the situation. Also, duration of symptoms
is brief in PBA, whereas a depressed mood typically lasts weeks
to months.
 The pathophysiology is not clear but is believed to be a disorder
of the cortico-pontine-cerebellar circuit. It is thought that
disruption here can lower the threshold for emotional
response.This disruption is believed to lead to the emotional
incongruent response.

70. Cont…
 Various agents including selective serotonin reuptake inhibitors
and tricyclic antidepressants have been used with varying
success to treat PBA.
 The combination of dextromethorphan with low-dose quinidine
has resulted in a treatment for patients with PBA. Its mechanism
of action is unknown.
 The recommended dosage is 1 capsule daily for 7 days followed
by 1 capsule every 12 hours beginning on day 8. Most patients
notice reduction in lability after 1 to 2 weeks of treatment.

71. References :
 Braddom's Physical Medicine and Rehabilitation - 5E
 Physical Medicine and Rehabilitation Board Review